Studies on neural transport mechanisms are here focussed on elucidating the reaction mechanism of the Na, K-ATPase. This enzyme functions in the plasma membrane as the cellular sodium pump, transporting Na out of and K into the cell. Through this action the Na, K-ATPase is involved not only in cellular homeostasis, but also in generating the resting membrane potential essential for the neural action potential as well as for many secondarily-active co-transport systems. Numerous suggestions relate disorders of enzymatic function to specific diseases (none proved), and the enzyme may serve as the receptor for the digitalis family of drugs and for proposed endogenous regulators. Here five areas of biochemical studies on the Na, K-ATPase are proposed, continuing and extending current investigations. (1) Studies on substrate sites are concerned with delineating the relationship between kinetically distinguishable high- and low-affinity sites, in terms of binding and kinetic experiments with various substrates, examining the differential effects of ligands and modifiers, and exploring the interactions between enzymne fluorescently labeled at the adenine-receptive site and fluorescent reagents that interact at the acyl phosphate hydrolytic site. (2) Studies on divalent cations are concerned with effects at sites beyond those at which Mg binds with ATP, sites at which conformational transitions may be modulated. These experiments include binding and kinetic studies, and exploration of the potential for exploiting rare earth cations as probes of these sites. (3) Studies on monovalent cation interations involve distinguishing among the various sites in terms of relative affinity and sidedness of accessibility, as well as the functional result on catalytic activity of their occupancy. (4) Studies on the reaction processes are concerned with synthesizing the binding and kinetic data on these sites with the properties of the various reactions catalyzed by the enzyme, in the form of quantitative models of the reaction process. (5) Studies on enzyme modification involve efforts to develop labels for the substrate and cation sites that can be used to identify those regions on the primary sequence.